Abstract

Previous reports have indicated that in vitro biliary clearance (Cl_biliary) determined in sandwich-cultured hepatocytes correlates well with in vivo Cl_biliary for limited sets of compounds. The purpose of this study was 1) to determine the in vitro Cl_biliary in sandwich-cultured human hepatocytes of angiotensin II receptor blockers and HMG-CoA reductase inhibitors that undergo limited metabolism and 2) to compare the predicted Cl_biliary values with estimated in vivo hepatic clearance data in humans. The average biliary excretion index and in vitro intrinsic Cl_biliary values of olmesartan, valsartan, pravastatin, rosuvastatin, and pitavastatin in sandwich-cultured human hepatocytes were 35, 23, 31, 25, and 16%, respectively, and 0.943, 1.20, 0.484, 3.39, and 5.48 ml/min/kg, respectively. Cl_biliary values predicted from sandwich-cultured human hepatocytes correlated with estimated in vivo hepatic clearance values based on published data (no in vivo data in humans was available for pitavastatin), and the rank order was also consistent. In conclusion, in vitro Cl_biliary determined in sandwich-cultured human hepatocytes can be used to predict in vivo Cl_biliary of compounds in humans.